Mass Balance and Pharmacokinetics of [14C]-CRN00808 in Healthy Volunteers

A Phase 1, Open-label, Two-cohort, Single Dose Study to Assess the Mass Balance, Route of Elimination, and Metabolic Profile of [14C] Labeled CRN00808 and Absolute Bioavailability of CRN00808 in Healthy Male Volunteers

A phase 1 healthy volunteer study to assess the mass balance, elimination, and metabolic profile of CRN00808. The study will be conducted in 2 parts: Part A, to characterize the absorption, distribution, metabolism, excretion, and mass balance of orally administered radio-labeled CRN00808; Part B, to determine the absolute bioavailability of CRN00808 administered using CRN00808 and radio-labeled CRN00808 as intravenous and oral forms.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [14C]-CRN00808; Drug: CRN00808

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • PRA Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male subjects 19 to 55 years of age
2. BMI 18 to 30 kg/m2

Exclusion Criteria:

1. Any uncontrolled or active major systemic disease including, but not limited to: acromegaly (with or without pituitary surgery or radiation therapy), cardiac, pulmonary, gastrointestinal, metabolic, urogenital, neurological, immunological, psychiatric, or neoplastic disorder with metastatic potential
2. History or presence of malignancy within the past 5 years. Subjects who have been successfully treated (for 3 months or longer) with no recurrence of basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix may be enrolled.
3. Use of any investigational drug within the past 60 days or 5 half-lives, whichever is longer
4. Have a medically significant abnormality observed during screening or the admission physical examination or in any other baseline measurements
5. Use of any prior medication without approval of the investigator within 14 days prior to admission
6. Tested positive at screening for HIV, hepatitis B surface antigen (HBsAg) or hepatitis C antibody (HCV-Ab) or has a history of a positive result
7. History of alcohol or substance abuse in the past 6 months
8. Any condition that in the opinion of the investigator would jeopardize the subject's appropriate participation in this Phase 1 study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A: [14C]-CRN00808 Oral Solution; Single oral dose of CRN00808 containing [14C]-CRN00808	Drug: [14C]-CRN00808; Investigational drug
Experimental: Part B: CRN00808 Oral Capsule w/ [14C]-CRN00808 IV microtracer; Single oral dose of CRN00808 followed by [14C]-CRN00808 IV microtracer injection	Drug: [14C]-CRN00808; Investigational drug; Drug: CRN00808; Investigational drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mass balance of CRN00808	Total radioactivity in urine and feces following a single oral dose [14C]-CRN00808 (expressed as a percentage of the total radioactive dose administered)	Up to 21 days (until >90% of dose is recovered)
Absolute bioavailability of CRN00808	Absolute bioavailability is calculated from the areas under the curve of intravenous and oral administration	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (AUC)	Assessment of the plasma area under the curve of CRN00808 and [14C]-CRN00808	Part A: Day 1 to day 21 (depending on recovery of dose). Part B: Day 1 through to Day 7
Pharmacokinetics (t1/2)	Assessment of the total elimination half-life of CRN00808 and [14C]-CRN00808	Part A: Day 1 to day 21 (depending on recovery of dose). Part B: Day 1 through to Day 7
Pharmacokinetics (Tmax)	Assessment of Time to attain maximum observed plasma concentration of CRN00808 and [14C]-CRN00808	Part A: Day 1 to day 21 (depending on recovery of dose). Part B: Day 1 through to Day 7
Pharmacokinetics (CL)	Assessment of the clearance of CRN00808 (Part B only)	Day 1 through to Day 7
Pharmacokinetics (CL/F)	Assessment of Apparent oral clearance of CRN00808	Part A: Day 1 to day 21 (depending on recovery of dose). Part B: Day 1 through to Day 7
Pharmacokinetics (Vz)	Assessment of Volume of distribution at terminal phase (Part B only)	Day 1 through to Day 7
Pharmacokinetics (Vz/F)	Assessment of Apparent volume of distribution at terminal phase	Part A: Day 1 to day 21 (depending on recovery of dose). Part B: Day 1 through to Day 7

Collaborators and Investigators

• Sponsor: Crinetics Pharmaceuticals Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2019
• Primary Completion (Actual): October 25, 2019
• Study Completion (Actual): October 25, 2019

Study Registration Dates

• First Submitted: January 14, 2020
• First Submitted That Met QC Criteria: January 27, 2020
• First Posted (Actual): January 29, 2020

Study Record Updates

• Last Update Posted (Actual): January 29, 2020
• Last Update Submitted That Met QC Criteria: January 27, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: CRN00808-06

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No